The support is to pay for educational materials on beverages and other nutrition issues. The way the general public is likely to see this deal is well captured by the first paragraph of coverage on NPR's health blog by Maggie Mertens:

When health questions crop up, the first resource for answers is often the family doctor. But if eating right is on your mind, how would you feel if the doctor's professional society is taking money from the soft-drink industry?

It is interesting to review the quotes in the blog coverage in which both AAFP and Coke try to defend this deal. Normal people, hearing those words come out of their mouths, would be clued into the fact that their having to say those words is a clear sign that something is rotten in Denmark. Yet they seem oblivious and somehow imagine that what they are saying actually constitutes a justification. They nicely illustrate the classic line from Upton Sinclair, "It is difficult to get a man to understand something when his salary depends upon his not understanding it."Coke CEO Muhtar Kent, writing recently in the Wall Street Journal: "Obesity is a serious problem," he wrote. "But are soft drinks the cause? I would submit to you that they are no more so than some other products -- and a lot less than many, many others." AAFP President Dr. Lori Heim: obesity is more complex and that "there's no one evil out there." Sure, she said, some people make "the wrong choices" on drinks. "But I have plenty of patients that even if they gave up sweetened beverages, it's what their forks are carrying that's the bigger problem."

Question number one: if this deal is on the up and up and AAFP retains strict scientific editorial control of these "educational" materials, then why does the statement by its president sound eerily like an echo of that of Coke's CEO? Question two: sure, obesity is complex, and it's precisely in the complexity that the danger lies. Even adopting a strictly scientific view, one can question whether we are over-vilifying the soft drink industry. Since you have a good deal of wiggle room with the science even when you have no commercial bias, as soon as you do have some commercial bias, then it is all that much more tempting to take advantage of the wiggle room. You can say, "Sure, sugary sodas help cause obesity, but so do potato chips, and since Coke gave us money, and the potato chip people didn't, then there's nothing scientifically wrong with shining the spotlight on the potato chips and giving Coke a little bit of a break." So then next year Frito-Lay comes after the AAFP with a "high six figure" deal. (By the way, AAFP, what kinds of pikers do you have for your negotiating team? Can't even get a cool million out of these guys? You look pretty sad compared to AMA and Sunbeam.) And now that Frito-Lay is paying the piper, well, suddenly, scientifically, it's not all that clear that it's either the soft drinks nor the potato chips that are the main cause of obesity; maybe it's those nasty fast food people. And next year McDonalds comes along with a deal. And so on. Now do you guys get it? (Pity the poor purveyor of calories that's last in line to buy off the AAFP.)

Final question: Why does the question of whether it's a good idea for AAFP to take money from Coke so quickly segue into the question of whether Coke is "evil"? (For our blogger colleague who likes logical fallacies, Roy Poses, this sounds like "straw man.") Why does it have to be: either they are evil or else it's just fine for us to take their money? What cannot it simply be that they have different interests--they are trying to make a buck selling beverages (some of which I enjoy drinking myself, I am pleased to report, if they don't have calories in them) while AAFP is trying to protect the public interest through credible health education? What part of conflict of interest don't you understand?

Addendum 10/30/09: For more on this development see a great commentary in the Columbia Journalism Review by Trudy Lieberman: http://www.cjr.org/campaign_desk/dr_cocacola_on_call.php?page=all. She notes that the press has been very slow to pick up this story, to her chagrin, but the Los Angeles Times did do an appropriate piece. She provides a great piece of historical background:

This is not the first time Coke has teamed up with a physician group, hoping to give its brand a clean bill of health. In 2003, Coca-Cola gave the American Academy of Pediatric Dentists $1 million. According to CSPI, before it got the money, the dental group spoke about the link between sugary drinks and dental disease. After the payment, the group’s president told reporters that the “scientific evidence is certainly not clear” about the role of soft drinks in causing poor oral health.

According to Lieberman, a family doc has started a petition on Facebook to complain. This reminds me that I am a bad boy as I have not directly written to the AAFP president, as a member, voicing my dissent. (And I just got my annual dues renewal notice from AAFP!)

This case has been getting tossed around since 1999. It defies a quick summation. An anesthesiologist then on the faculty at Columbia University, Elliott Bennett-Guerrero, received funding from Abbott Laboratories to do a study of several blood-expanding intravenous solutions--fluids that were supposed to treat blood loss and shock without the need for a blood transfusion. One ingredient in one of the fluids was hetastarch, which had long been known to trigger serious bleeding. Abbott apparently hoped that a new formulation of hetastarch would minimize the bleeding risks. However, the consent form administered to research subjects failed to reveal the known bleeding risks associated with hetastarch. A number of research subjects then developed serious bleeding problems during or after open-heart surgery.

Columbia conducted several internal investigations, and has just been ordered by the US government Office of Human Research Protections to go back and notify all surviving subjects of the risks they had faced.

As I say, the case is a convoluted one, but I would offer the following observations to accompany the investigative work of Lenzer-Brownlee:

The process of informed consent is supposed, at a minimum, to include mention of those harms and benefits the reasonable patient would wish to know about prior to deciding whether or not to accept the offered treatment. An increased risk of bleeding, to the extent of possibly needing a transfusion, would seem clearly to be among those harms. The standard for consent requires that for (nonexperimental) medical treatment. If the treatment is administered within the context of a research study, the threshold for adequate disclosure of information about harms and benefits is increased. This is because the fact that one’s personal physician is prescribing treatment for the patient’s benefit, is presumed to act as a safeguard to the patient’s welfare in the therapeutic setting. In the research setting, where the treatment might be assigned via an impersonal protocol randomly, this safeguard is absent; hence the need for even stricter disclosure of risks.

Commercial sponsorship of a research trial raises a couple of questions in this setting. If Abbott paid for the study via an “unrestricted” grant, did they also supply the consent form language? If so the language might have been slanted so as to increase the rate at which subjects were enrolled and to complete the trial faster, a common concern in the industry; the language would not necessarily have been slanted to maximize subject protection. Reportedly Dr. Bennett-Guerrero was conducting 25 trials at the same time. Can a single physician properly supervise that many trials at once, or was this an example of a faculty member trying to maximize revenue on behalf of the institution, or in pursuit of his own interests, or both?

Finally, when asked about the harms suffered by some patient/subjects, the investigator reportedly said that this could not be proven, because the study was underpowered. (That is, there were too few subjects in each category, to show a risk of being harmed at a level that reached statistical significance.) Why was an underpowered study being done in the first place? A study that enrolls too few subjects in toto to answer the scientific question it is supposed to answer is scientifically worthless, and therefore the subjects who were put at risk ran that risk or no good scientific reason. No research review board should approve such a study. Alternatively, was Columbia merely a single site of a multisite trial (so that there were too few subjects at Columbia, but that the total number of subjects was sufficient)? If it was, what arrangements were made to assure that investigators (and review boards) at one site, learned of harms to subjects that might occur at another site? How much of the study data were available for review by the investigator at each individual site? In other trials that have attracted criticism, the industrial sponsor has viewed the trial data as its proprietary information, and has refused to release it to individual investigators; this has compromised the ability of the investigator to protect the interests of subjects as well as to interpret the data and to assure that what is eventually published is true.

Sunday, October 4, 2009

Warning to regular readers-- this is a very long post and is only peripherally related to the main theme of this blog. However it is also an important post as it deals with questions about the accuracy of a previous statement made here, and raises questions of what is the most suitable way to correct any such inaccuracies. I do want it to be known that I try to take very seriously my obligation to provide accurate information here and to cross-check facts before posting.

Since I posted my comment on Sept. 23, regarding the article on flu vaccines by Dr. Juan Gervas on the Healthy Skepticism (HS) website, I have been in nearly continuous contact with Dr. Peter Mansfield, the Australian GP who's director of HS. Dr. Mansfield has been concerned about inaccuracies in my post and has been trying to persuade me to approach them in the way that he has specified, for various reasons having to do with HS's, my, and Dr. Gervas's reputation. I made two counteroffers which seemed to me to be quite reasonable. First, I expected that anyone who disagreed with the content of any of my posts (such as "Anonymous" did right away in this case) could simply do what "Anonymous" actually did do, and post a comment. I do not delete any comments from this blog unless they are commercial in nature or else completely vulgar and irresponsible. Second, when Dr. Mansfield elected not to post a comment, the very high regard in which I hold him and HS prompted me to offer to publish a post of his own composition in which he explained all the inaccuracies that he thought to be present in my original post. Again, for reasons too complex to review here, he chose not to do that either, except as a very last resort.

Dr. Mansfield continued to insist that the only satisfactory way to deal with this would be for me, first, to go over Dr. Gervas's original article sentence by sentence and explain any disagreements that I had with it, documenting each; and next, that I do the same thing subsequently with my own post. To which I replied that this might indeed be an ideal exercise but that I did not have time to do that. Unfortunately the amount of time I have subsequently taken in discussing this back and forth with Dr. Mansfield has now been several times what it would have taken me to do what he asked up front. So, as a compromise, I will here do a passage-by-passage re-analysis of my own post of Sept. 23. I am aided in this process by a message Dr. Mansfield sent me in which he offered his own such analysis. (As I said, that is what I offered to print verbatim, with an explanatory introduction, but that he requested that I not).

What follows is the original post with my later comments in bold italics.

Unhealthy Skepticism about Flu ImmunizationsHealthy Skepticism is a website that I have been proud to be a member of and that assisted me greatly in all of my research. I am a member of HS and also of a listserv that includes HS members and generally find it highly informative. So it pains me to have to dissociate myself from a recent thread on that listserv and website that I believe to be quite wrong.

Dr. Mansfield notes that I am not "associated" with the article by Dr. Gervas, as it was clearly written by him and is not an official statement of HS as an organization, so there is no need to "dissociate" myself from it. However, others have fallen into the same trap that I did in assuming that the prominence that the article received (being translated into six languages for example) suggested some degree of HS endosement of the statement. I will address the HS listserv issue below.

I am taking this public stance because I think the issue holds lessons for us Pharmascolds, in terms of how we can go too far in our opposition to the bad practices of the pharmaceutical industry.

Dr. Mansfield here takes issue with my characterization of Dr. Gervas's article and notes that Dr. Gervas does not "go too far" or complain about misdeeds of Pharma. However my own language was very careful. I did not say Dr. Gervas said these things. I said that the issue raises these concerns in a general way. In effect I said that Dr. Gervas's article offers a teachable moment to address these issues of general concern. (Why of general concern I'll explain later as well.)

My concern is with a piece posted on the HS site, "In the Face of Swine Flu, Common Sense and Science": http://www.healthyskepticism.org/news/2009/Oct09.phpThe author is a Spanish GP who also holds a couple of academic posts. As a family physician I have been on the receiving end of attacks due to having dared to speak out on medical issues, when the relevant subspecialists thought that only they were entitled to express opinions. So I might have been expected to immediately identify with the author.

It was unkind of me not to mention Dr. Juan Gervas by name in this part of the post, though of course I did offer the direct link to his article.

The basic thrust of the piece is that swine flu is an example of "disease mongering"; that the vaccine is unnecessary because the disease is very mild; the vaccine has been rushed into production and so cannot be known to be safe; and anyway, the seasonal flu vaccine has been overpromoted and is not really scientifically shown to be of benefit.

Dr. Mansfield has pointed out to me that here I have been guilty of smooshing together what Dr. Gervas said in this specific article and what he had said elsewhere on the HS listserv. The agreement about this listserv is that what goes on there stays there unless we ask explicit permission to reprint something. So it was out of line for me to use the words "disease mongering," and I apologize for that. Dr. Gervas, interestingly enough, is not blaming the drug industry for any disease mongering or overselling of vaccines and antivirals; he is rather pointing the finger at WHO and national public health authorities. On that point I should have been more accurate in characterizing his position. Dr. Mansfield takes issue with several other points in my brief summary of what Dr. Gervas said. I invite any reader to go to Dr. Gervas's article and form your own opinion of the relative accuracy or inaccuracy of my summary.

Let me separate my reactions into two parts--seasonal flu and swine flu.I have followed the literature for many years on the health benefits of seasonal flu vaccines. (I personally always get my flu shot each fall, even though I am not now doing direct patient care.) I have been impressed with the nearly uniform showing in all studies that flu vaccines are highly beneficial and highly cost-effective. Indeed it is one of the most cost-effective preventive interventions available to us.

Dr. Mansfield disagrees and wants to know why I did not offer evidence in support of my assertions here. He particularly questions the claim that flu vaccine for healthy adults is cost-effective. I went back and looked at two sources-- Cochrane reviews of the effectiveness of flu vaccines; and articles included in Rick Bukata and Jerry Hoffman's "Primary Care Medical Abstracts" over the past 5 years. Without spending a lot of time here on this blog, which is not about seasonal flu vaccines, I think a case can be made that the seasonal flu vaccine is cost-effective for higher-risk patients, and less so, but still of value, for lower-risk patients. The dispute seems mostly to be over the quality of the studies, as there are many observational studies rather than randomized trials in the mix. On the other side of the coin is the undeniable fact that a flu shot is 1) incredibly safe and 2) very cheap. That means that for it to be cost-effective requires that a relatively low threshold of evidence be met. I would agree with both Dr. Mansfield and the Cochrane people that ideally, studies of better quality would be done in the future.

So trying to cast doubt on the wisdom of a swine flu vaccine by attacking the benefits of the regular seasonal vaccine seems completely wrong-headed.

Dr. Mansfield regards this statement as not reasonable because it is "vague and abusive." I do not think it is an inaccurate characterization of Dr. Gervas's argument. Again the reader can read both and decide.

As to the swine flu, we charge the public health authorities with preparing a vaccine each year that will protect us from the dominant strain of flu that is going to appear in the fall. This year, the appearance of a novel strain of H1N1 flu (swine) created great concern because most Americans under age 60 have never been exposed to a similar flu virus, so natural immunity was thought to be very low. And indeed, at this time in the U.S., there are near-epidemic levels of flu, very unusual for this early in the fall, and more than 90 percent of it is H1N1 (though when they started making the vaccine, no one could have known this would necessarily happen). Every year the task of making the flu vaccine with the correct strains of antigen is a crap shoot and any year you could guess wrong.

Dr. Mansfield thought this statement generally correct, but did not see it as being at odds with the general tenor of Dr. Gervas's piece. Frankly I am puzzled. I take Dr. Gervas to be saying in part that because the H1N1 flu is such a mild disease, calls for massive use of a vaccine against it are inappropriate. So what I say here seems at least somewhat contrary to the tenor of his thought. In recent weeks additional evidence of the severity of H1N1 in the US, especially among pregnant women (though again, strict comparisons with the mortality due to seasonal flu should be kept in mind), has come forward. I put that aside as no such evidence was available to Dr. Gervas at the time he wrote his article. Also I am focusing on events in the US whereas he would naturally be more concerned about what is happening in Spain, which might be quite different. (I have not researched that.)

The swine flu is being manufactured using the same techniques as used for the seasonal flu, which has an excellent safety track record ever since 1976, the year of the last swine flu scare.

Dr. Mansfield says this statement is inaccurate and mentions such things as the adjuvant added in some countries. I am again guilty of speaking to the US situation rather than the international situation, and I regret that narrowness of vision. I stand by what I say as accurate for the US. I should mention that our bioethics group has recently been asked to prepare a report on the ethics of allocating flu vaccines for the state of Texas, so I have been paying more attention than usual to the vaccine issue and also consulting with some vaccine experts locally. I realize now that I should mention this as a potential conflict of interest as our group is to be paid by the state department of health for our report.

In short I see no reason whatever to interpret anything related to swine flu vaccination as a public health response, as somehow related to disease mongering by the pharmaceutical industry or its allies or shills.

Ditto as above-- this relates more to what was on the HS listserv than what was in Dr. Gervas's article and I should not have used those terms. Plus, again, Dr. Gervas does not point a finger at the industry.

Now, where the author of the HS piece questions the use of antivirals, I think he is on firmer ground. Antivirals for flu have in the past been significantly overpromoted.

No serious dispute here.

The HS piece ends with this language:"Note: The only purpose of the author is to transmit the best knowledge about the problem at present, and for that he has reviewed the world literature. This text is an informative one, not for clinical use. Sadly, the information you can obtain from others sources (public organizations, scientific societies, media) is very different; they will know why."This appears to be a gratuitous ad hominem attack on anyone who disagrees with this author's conclusions, and seems utterly uncalled for.

Dr. Mansfield notes one again that it is not an "HS piece" but Dr. Gervas's piece published by HS; and he views my condemnation of the language as "unreasonable." Here I stand fully by my original statement. I found this an offensive and unnecessary ad hominem suggestion that the motives of others might be less pure than his own. My friend the vaccine expert similarly singled this passage out from the rest of the article as an uncalled for affront.

I may add that I checked into a couple of the authors' citations, and was impressed that the conclusions reached by those articles did not square with the conclusions offered in the HS piece.

Dr. Mansfield notes that this is inaccurate because there were NO citations as such in Dr. Gervas's piece. That is true and I apologize for my inaccurate characterization. His list of references was a bibliography, not citations. However, I did look at two of the references listed, that seemed pertinent to his arguments, and did not find as much support for his arguments therein as I would have guessed from his article.

So why do I make a big deal of my personal disagreement with this particular piece of writing (one that HS was apparently proud enough of, to have translated into several languages for dissemination)? Again, I need to beware attributing motives to others. But we have to be very cautious that our distrust of the drug industry and its many devious and dishonest practices, and of our physician colleagues who eagerly do the industry's bidding, not spill over into areas where it does not belong. When we decide that any product manufactured by the drug industry is therefore unsafe or unneeded; or that any effort to raise public concern about a disease is therefore commercialized disease-mongering, then I think we have clearly crossed over that line.

Again, Dr. Mansfield states that nowhere did Dr. Gervas actually commit any of these offenses. I would again say that my intent was to raise the issue and use his article as a teachable moment, not to claim that he had personally done these things. I was influenced in so doing by having read a recent article by Melissa Healy in the Los Angeles Times, on why parents in California were reluctant to have their children get the H1N1 vaccine. Distrust of the drug industry was one of the reasons given. Where does that leave people like me who arguably help to spread distrust of the drug industry? I certainly share Dr. Gervas's hopes that H1N1 will turn out to be mild and we will see our vaccination efforts in hindsight as excessive. But if children die in California because of an attitude that I helped to spread, then I worry about the misapplication of what people like me (even if not like Dr. Gervas) say. (Dr. Gervas did, however, say very clearly that the vaccine was experimental and untested and that the disease itself was very mild--so any parent reading his article would be inclined not to want his/her child vaccinated.)I do want to stress that Dr. Gervas is no doubt better read than I on the subject of flu and flu vaccines, so he may well be correct and I incorrect. I am delighted that HS published his piece so that we could all double check on the degree to which recommendations are evidence-based.

The editorial referred to the previous Globe news article--http://www.boston.com/news/health/articles/2009/09/29/60_doctors_took_speaker_fees_from_drug_giant/?page=full--in which Liz Kowalczyk reported, "At least 60 Massachusetts doctors collectively have earned more than a half-million dollars this year as speakers paid by pharmaceutical giant Eli Lilly & Co. - including two Boston Medical Center physicians whose participation is being reviewed for possible violation of a hospital policy against marketing activities by its doctors." She further explained that Lilly is out ahead of other drug companies in releasing these data, but that as of next July, all drug companies will be required to reveal this information under the new sunshine law in effect in Massachusetts.

Boston Medical Center has a policy that their faculty physicians should give talks only if they determine the content. Kowalczyk added, "In e-mailed statements, the doctors defended their talks. [Dr. Elliot] Sternthal said he determines 'the structure of the presentation by my choice of disease state and clinical trial slides, order of presentation and emphasis of teaching points. This is in compliance with BU/BMC policy.’"

Dr. Sternthal's insistence that he's a good guy because even though he receives his slides and talking points from the drug firm, he decides all by himself how to tweak the talk, reminded me of a sad spectacle at my own medical center a few years ago. We held a panel on the ethics of taking stuff from the drug companies, and the majority of the panelists spoke in favor of a laissez-faire relationship with industry. (That was before our medical school adopted a strict policy banning most gifts.) Several of the panelists admitted to being on speakers' bureaus and "tweaking" talks much the way Dr. Sternthal claimed. "Yes, I use their slides," said one, "but I always throw in some of my own observations."

Unfortunately I was slow out of the starting block at that panel, or else I could have asked the panelists who were preening themselves on their editorial independence if they had talked with their lawyers about possible Federal prosecution.

Dr. Gleason took money for speaking for Jazz Pharmaceuticals and adding his own medical opinions to the scripted talks he was provided. Like my colleagues on the panel, he assumed that was what scientifically trained physicians are supposed to do--supplement any canned talk with their own clinical observations and knowledge. Unfortunately some of his so-called "knowledge" included using the drug for off label purposes.

The drug company is legally prohibited from marketing a drug for off label use. Dr. Gleason figured that as he was a physician, and could legally prescribe the drug for anything he wanted, he could also talk about off label uses.

Not so, said the federal agents in suits who surrounded and handcuffed him at a train station. So far as they were concerned, he took the drug company's money, and so he was a drug company employee. Jazz Pharmaceuticals pointed out to him that they gave him a script to follow, and he refused to follow the script, so as far as his legal hassle was concerned, he was on his own.

The Gleason case puts the dilemma of the speakers-bureau physician neatly in a nutshell. If you exactly follow the script, you're clearly nothing but a shill for the company, and ought not to be able to hold your head up in polite medical society. If you insist on giving your own spiel, and don't follow the script--but take the company money anyway--the Feds may be after you with handcuffs.

And so, concluded the Globe editorial very reasonably, "When doctors promote drugs in exchange for pay from pharmaceutical companies, they cease to be independent evaluators of the risks posed by those drugs, and they cease to be unbiased caregivers for their patients. Hospitals should prohibit doctors from taking part in so-called speakers bureaus, whereby companies compensate them for giving talks to colleagues about new drugs. Legislators should go beyond requiring disclosure of the relationships, and ban the practice."My only question is why we doctors should have to have hospitals and legislators tell us what's ethical.

Novartis is implanting a chip in people's shoulders that will call their cell phone if they are late taking their next dose of Diovan for their high blood pressure. So far 20 people have been experimented on and the company is ecstatic that this has improved compliance from 30 to 80 percent.

When I first read this quickly I thought that they had figured out a chip that would measure blood pressure and let you know that your blood pressure was too high. Sadly the chip is not that smart. Novartis puts one chip in your shoulder and a second chip inside each pill (great way to reduce the excessive costs of medicines, guys). The chip in (on?) your shoulder waits to see the other chip go by and if none pass along withion the specified time period, ring goes the phone. This by the way has important health implications. What if your doc has miscalculated your dose and the Diovan is actually making your blood pressure go so low you're about to pass out? The dutiful chips still keep bugging you to take the next pill. Too bad they won't call 911 for you when you're stretched out on the floor.

Now, I freely admit that not taking your pills (compliance, adherence, or the term du jour) is a super big problem in chronic illnsesses like hypertension; and treating hypertension is truly lifesaving. So what's the beef with this really cute little chip, all references to 1984 aside? And assuming both previous and future patients give appropriate informed consent to have the chip implanted?

My main thought is that Diovan is an expensive, on-patent anti-hypertensive, that in the grand scheme of things ought to be a third-line treatment for hypertension at best. So who is implanting chips to remind people to take their generic diuretic; or their generic beta blocker; or their generic ACE inhibitor? Why is the chip only available to remind people to take the drug that most of them have no reason to be on in the first place, were it not for slick marketing?

If the chip were coming from a reasonably unbiased public health source, and aimed solely at reducing morbidity and mortality from hypertension, then we could focus our concerns on issues like privacy and so on. Given that the chip-pushers are motivated by corporate profit much more than by public health, we have other concerns to address first.